This project aims to understand the role and mechanism of function of HIV regulation in the virus life cycle and disease development; and to dissect the mechanisms of nucleocytoplasmic trafficking of macromolecules. The conclusions of this work are also applied towards the design of better vaccine approaches against AIDS. We have focused our studies in this period on the interactions of Rev and Vpr with cellular components; and on the further understanding of posttranscriptional regulation and nucleocytoplasmic export, which are important steps in the process of gene expression. Our results contribute significantly to the further understanding of the basic mechanisms of nucleocytoplasmic traffic of macromolecules. The understanding of the regulatory mechanisms of HIV gene expression has many important practical applications. We have applied this knowledge to the development of improved DNA vaccination approaches.